Conectividad funcional a partir de la perfusión cerebral en pacientes epilépticos y con enfermedad de Parkinson / Functional connectivity from cerebral perfusion in patients with epilepsy and Parkinson's disease

Introducción: La epilepsia y la enfermedad de Parkinson han sido descritos como trastornos de redes neurales. El estudio de la conectividad por modalidades moleculares puede ser más relevante fisiológicamente que los basados en señales hemodinámicas. Objetivo: Proponer una metodología para la descripción de patrones de conectividad funcional a partir de la perfusión cerebral por tomografía por emisión de fotón único. Métodos: La metodología incluye cuatro pasos principales: preprocesamiento espacial, corrección del volumen parcial, cálculo del índice de perfusión y obtención de la matriz de conectividad funcional mediante el coeficiente de correlación de Pearson. Se implementó en 25 pacientes con distintos trastornos neurológicos: 15 con epilepsia farmacorresistente y 10 con enfermedad de Parkinson. Resultados: Se encontraron diferencias significativas entre los índice de perfusión de varias regiones de los hemisferios ipsilateral y contralateral tanto en pacientes con epilepsia del lóbulo frontal como en pacientes con epilepsia del lóbulo temporal. Igual resultado se obtuvo en los pacientes con enfermedad de Parkinson con distintos estadios de la enfermedad. Para cada grupo se identificaron patrones de conectividad funcional que involucran a regiones relacionadas con la patología en estudio. Conclusiones: Con el desarrollo de esta metodología se ha demostrado que la tomografía por emisión de fotón único aporta información valiosa para estudiar la organización de las redes funcionales del cerebro. Futuras investigaciones con mayor número de pacientes contribuirían a hacer inferencias sobre los correlatos neurales de los distintos trastornos cerebrales(AU)

Introduction: Epilepsy and Parkinson's disease have been described as disorders of neural networks. The study of connectivity by molecular modalities may be more physiologically relevant than those based on hemodynamic signals. Aim: The aim of the present work is to propose a methodology for the description of functional connectivity patterns from brain perfusion by single photon emission tomography. Methods: The methodology includes four main steps: spatial preprocessing, partial volume correction, calculation of the perfusion index and obtaining the functional connectivity matrix using Pearson's correlation coefficient. It was implemented in 25 patients with different neurological disorders: 15 with drug-resistant epilepsy and 10 suffering Parkinson's disease. Results: Significant differences were found between the perfusion indexes of various regions of the ipsilateral and contralateral hemispheres in both patients with frontal lobe epilepsy and patients with temporal lobe epilepsy. The same result was obtained in Parkinson's disease patients with different stages of the disease. For each group, functional connectivity patterns involving regions related to the pathology under study were identified. Conclusions: With the development of this methodology, it has been demonstrated that single photon emission tomography provides valuable information to study the organization of functional brain networks. Future research with a larger number of patients would contribute to make inferences about the neural correlates of the different brain disorders(AU)

Massive cerebral air embolism following percutaneous transhepatic biliary drainage: A case report.

RATIONALE: Cerebral air embolism from portal venous gas rarely occurs due to invasive procedures (e.g., endoscopic procedures, liver biopsy, or percutaneous transhepatic biliary drainage) that disrupt the gastrointestinal or hepatobiliary structures. Here, we report a rare case of fatal cerebral air embolism following a series of percutaneous transhepatic biliary drainage tube insertions. PATIENT CONCERNS: A 50-year-old woman with a history of cholecystectomy, liver wedge resection, and hepaticojejunostomy for gallbladder cancer presented with altered mental status 1 week after percutaneous transhepatic biliary drainage tube placement. DIAGNOSES: Extensive cerebral air embolism and acute cerebral infarction. INTERVENTIONS: Brain computed tomography and magnetic resonance imaging, hyperbaric oxygen therapy, medical therapy. OUTCOMES: Despite the use of hyperbaric oxygen therapy and medical treatment including vasopressors, the patient eventually died due to massive systemic air embolism. LESSONS: To date, there have been no reports of cerebral air embolism due to percutaneous transhepatic biliary drainage with pronounced radiologic images. We reviewed previously reported fatal cases associated with endoscopic hepatobiliary procedures and assessed the possible mechanisms and potential causes of air embolism.

Effect of Recanalization on Cerebral Edema, Long-Term Outcome, and Quality of Life in Patients with Large Hemispheric Infarctions.

OBJECTIVES: Space-occupying cerebral edema is the main cause of mortality and poor functional outcome in patients with large cerebral artery occlusion (LVO). We aimed to determine whether recanalization of LVO would augment cerebral edema volume and the impact on functional outcome and quality of life (QoL). MATERIALS AND METHODS: Prospectively, 43 patients with large middle cerebral artery territory infarction or NIHSS ≥ 12 on admission were enrolled. The degree of recanalization (partial and complete versus no recanalization) was assessed by computed tomography (CT)-angiography or Duplex ultrasound more than 24 h after symptom onset. Cerebral edema volume was measured on follow up CTs by computer-based planimetry. Mortality, functional outcome (by modified Ranking Scale (mRS) and Barthel Index (BI)) were assessed at discharge and 12 months, and QoL (by SF-36 and EQ-5D-3L) at 12 months. RESULTS: Mean cerebral edema volume was 333±141 ml without recanalization (n=13, group 1) and 276±140 ml with partial or complete recanalization (n=30, group 2, p= 0.23). There were no significant differences in mortality at discharge (38% versus 23%), at 12 months (58% versus 48%), in functional outcome at discharge (mRS 0-3: 0% both; mRS 4-5: 62% versus 77%) and at 12 months (mRS 0-3: 0% versus 11%; mRS 4-5: 42% versus 41%). The BI improved significantly from discharge to 12 months only in group 2 (p=0.001). Mean physical component score in SF-36 was 25.6±6.4, psychological component score was 41.9±14.1. In the EQ-5D-3L, most patients reported problems with activities of daily living, reduced mobility, and selfcare. CONCLUSIONS: Recanalization of a large cerebral artery occlusion in the anterior circulation territories is not associated with amplification of post-ischemic cerebral edema but may be correlated with better long-term functional outcome. QoL was low and mainly dependent on physical disability. The association between recanalization, collateral status and development of cerebral edema after LVO and the effect on functional outcome and quality of life should be explored in a larger patient population.

Poor Outcomes Related to Anterior Extension of Large Hemispheric Infarction: Topographic Analysis of GAMES-RP Trial MRI Scans.

BACKGROUND: We aimed to assess the correlation of lesion location and clinical outcome in patients with large hemispheric infarction (LHI). METHODS: We analyzed admission MRI data from the GAMES-RP trial, which enrolled patients with anterior circulation infarct volumes of 82-300 cm3 within 10 hours of onset. Infarct lesions were segmented and co-registered onto MNI-152 brain space. Voxel-wise general linear models were applied to assess location-outcome correlations after correction for infarct volume as a co-variate. RESULTS: We included 83 patients with known 3-month modified Rankin scale (mRS). In voxel-wise analysis, there was significant correlation between admission infarct lesions involving the anterior cerebral artery (ACA) territory and its middle cerebral artery (MCA) border zone with both higher 3-month mRS and post-stroke day 3 and 7 National Institutes of Health Stroke Scale (NIHSS) total score and arm/leg subscores. Higher NIHSS total scores from admission through poststroke day 2 correlated with left MCA infarcts. In multivariate analysis, ACA territory infarct volume (P = .001) and admission NIHSS (P = .005) were independent predictors of 3-month mRS. Moreover, in a subgroup of 36 patients with infarct lesions involving right MCA-ACA border zone, intravenous (IV) glibenclamide (BIIB093; glyburide) treatment was the only independent predictor of 3-month mRS in multivariate regression analysis (P = .016). CONCLUSIONS: Anterior extension of LHI with involvement of ACA territory and ACA-MCA border zone is an independent predictor of poor functional outcome, likely due to impairment of arm/leg motor function. If confirmed in larger cohorts, infarct topology may potentially help triage LHI patients who may benefit from IV glibenclamide. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01794182.

Avaliação da resposta hemodinâmica cerebral através da monitorização com a espectroscopia próxima ao infravermelho (NIRS) em pacientes com doença aterosclerótica da artéria carótida submetidos a endarterectomia / Evaluation of the brain hemodynamic response by means of near-infrared spectroscopy (NIRS) monitoring in patients with atherosclerotic carotid disease undergoing endarterectomy

Resumo Contexto A espectroscopia próxima ao infravermelho (NIRS) é uma técnica não invasiva que detecta as alterações hemodinâmicas teciduais. A NIRS pode monitorar de forma contínua as informações fisiológicas vasculares intracranianas. Por ser portátil, ela pode ser utilizada à beira do leito e no centro cirúrgico. Objetivos Avaliar as possíveis alterações hemodinâmicas cerebrais durante a endarterectomia em pacientes com estenoses maiores que 70% utilizando NIRS. Métodos Foram avaliados 10 voluntários portadores de doença carotídea aterosclerótica com indicação de endarterectomia. Após a seleção dos pacientes, que responderam um questionário com dados epidemiológicos e informações referentes à presença de comorbidades, a doença foi confirmada por métodos diagnósticos. No procedimento cirúrgico, utilizou-se a NIRS para monitorização. Foram avaliadas as variáveis saturação de oxigênio (SatO2), hemoglobina total (HbT), hemoglobina reduzida (HbR) e hemoglobina oxigenada (HbO) nos três tempos cirúrgicos pré-, trans e pós-clampeamento carotídeo. Utilizou-se p < 0,05 como nível de significância. Resultados A avaliação dos resultados obtidos por meio das medidas registradas pela NIRS permite afirmar que HbR e SatO2 variam ao longo das etapas da cirurgia. Durante o clampeamento, a variável HbR mostra valores mais elevados que nas outras duas etapas da cirurgia. Por outro lado, a variável SatO2 mostra redução durante o clampeamento. Conclusões A NIRS é um método viável e aplicável de monitorização intracerebral, não invasivo e em tempo real, durante a endarterectomia carotídea, capaz de medir de forma precisa as mudanças das condições hemodinâmicas capilares intracerebrais.

Abstract Backgrounds Near-infrared spectroscopy (NIRS) is non-invasive technique that detects hemodynamic alterations in tissues. It enables continuous monitoring of intracerebral vascular physiologic information. Due to its portable nature, NIRS may be used bedside or in the operating room. Objectives To evaluate use of NIRS for intraoperative monitoring of the brain hemodynamic response, during carotid endarterectomy. Methods 10 patients with atherosclerotic carotid disease scheduled for endarterectomy were evaluated. After patients had been selected, they answered a questionnaire on epidemiological data and information about comorbidities and then carotid disease was confirmed with diagnostic methods. NRIS monitoring was used during the surgical procedure. The variables analyzed before, during and after carotid clamping were oxygen saturation (SatO2), total hemoglobin (THb), reduced hemoglobin (RHb), and oxyhemoglobin (OHb). A p value of <0.05 was considered statistically significant. Results The results obtained from NIRS show that RHb and SatO2 vary during the different stages of surgery. RHb levels are higher during clamping, when compared with the other two surgical stages. On the other hand, SatO2 is lower during clamping. Conclusions During carotid endarterectomy, NIRS is a feasible, real-time, and non-invasive intracranial monitoring method that accurately and reliably measures the changes in intracerebral capillary hemodynamic conditions.

Remote ischemic conditioning enhances heart and brain antioxidant defense / Condicionamento isquêmico remoto melhora a defesa antioxidante do coração e do cérebro

Abstract Background Ischemia-reperfusion injury contributes to morbidity after revascularization procedures. Along with early reperfusion, tissue conditioning by alternating intervals of brief ischemia-reperfusion episodes is considered the best approach to limit tissue damage. Remote ischemic conditioning is conducted remotely, in tissues other than those under ischemia. Despite this, remote ischemic conditioning protection mechanisms are poorly understood, which can lead to misapplication. Objectives To assess whether remote ischemic conditioning works in the heart and brain through enhancement of cells' antioxidant defenses and whether the response is sustained or temporary. Methods Twenty-one male Wistar rats were assigned to three groups (n = 7): SHAM: same procedure as the other groups, but no remote ischemic conditioning was carried out. RIC 10: heart and brain were harvested 10 minutes after the remote ischemic conditioning protocol. RIC 60: heart and brain were harvested 60 minutes after the remote ischemic conditioning protocol. The remote ischemic conditioning protocol consisted of 3 cycles of 5 min left hindlimb ischemia followed by 5 min left hindlimb perfusion, lasting 30 min in total. Heart and brain samples were used to measure the tissue antioxidant capacity. Results Remote ischemic conditioning increased heart and brain antioxidant capacity after 10 minutes (0.746 ± 0.160/0.801 ± 0.227 mM/L) when compared to SHAM (0.523 ± 0.078/0.404 ± 0.124 mM/L). No enhancement of heart or brain antioxidant capacity was detected 60 minutes after remote ischemic conditioning (0.551 ± 0.073/0.455 ± 0.107 mM/L). Conclusions Remote ischemic conditioning temporarily enhances heart and brain antioxidant defenses in male Wistar rats.

Resumo Contexto A lesão de isquemia e reperfusão contribui para a morbidade após procedimentos de revascularização. Juntamente com a reperfusão precoce, o condicionamento tecidual através de breves episódios de isquemia e reperfusão é considerado a melhor abordagem para limitar o dano tecidual. Apesar disso, os mecanismos do condicionamento isquêmico remoto são pouco compreendidos, o que pode levar a uma aplicação incorreta. Objetivos Avaliar se o condicionamento isquêmico remoto funciona no coração e no cérebro através do aprimoramento da defesa antioxidante das células e se é uma resposta sustentada ou temporária. Métodos Vinte e um ratos Wistar foram divididos em três grupos (n = 7): SHAM, no qual não foi realizado condicionamento isquêmico; RIC 10, no qual 10 minutos após o protocolo de condicionamento isquêmico, foi realizada a coleta dos órgãos; e RIC 60, no qual 60 minutos após o protocolo de condicionamento isquêmico, foi realizada a coleta dos órgãos. O protocolo de condicionamento isquêmico remoto consistiu em três ciclos de 5 minutos de isquemia, seguidos de 5 minutos de perfusão no membro posterior esquerdo, com duração total de 30 minutos. Amostras foram usadas para medir a capacidade antioxidante do tecido. Resultados O condicionamento isquêmico remoto aumentou a capacidade antioxidante do coração e do cérebro após 10 minutos (0,746 ± 0,160/0,801 ± 0,227 mM/L) quando comparado ao SHAM (0,523 ± 0,078/0,404 ± 0,124 mM/L) . Sessenta minutos após o condicionamento isquêmico remoto, não foi detectado aumento da capacidade antioxidante do coração ou do cérebro (0,551 ± 0,073/0,455 ± 0,107 mM/L). Conclusões O condicionamento isquêmico remoto melhora temporariamente as defesas antioxidantes do coração e do cérebro em ratos Wistar.

Overexpression of calcitonin gene-related peptide protects mouse cerebral microvascular endothelial cells from high-glucose-induced damage via ERK/HIF-1/VEGF signaling.

In the diabetic brain, hyperglycemia damages the cerebrovasculature and impairs neurovascular crosstalk. Calcitonin gene-related peptide (CGRP) is an important neuropeptide that is active in the vascular system. In this study, we aimed to investigate whether CGRP is involved in the high-glucose-induced damage in mouse cerebral microvascular endothelial (b.END3) cells and the possible mechanism in vitro. The overexpression of CGRP by lentiviral transduction inhibited cell apoptosis but not proliferation. In contrast to the promoting of angiogenesis and migration under normal glucose, CGRP inhibited hyperglycemia-induced tube formation but had no effect on migration. Calcitonin gene-related peptide partly reduced the increased level of intracellular reactive oxygen species (ROS) and altered nitric oxide synthase mRNA expression. Furthermore, CGRP suppressed the increased HIF-1α/VEGF-A expression and the phosphorylation of ERK1/2 in hyperglycemia. The ERK inhibitor U0126 showed similar inhibition of cell apoptosis, tube formation and HIF-1α/VEGF expression as that exhibited by lenti-CGRP. These findings demonstrate the protective role of CGRP overexpression against high-glucose-induced cerebrovascular changes in b.END3 cells, possibly through the inhibition of ERK/HIF-1/VEGF signaling.

A clinical research on the potential pathogenesis of somatic cancer related cerebral venous sinus thrombosis.

To investigate the pathogenesis of somatic solid cancer-related cerebral venous sinus thrombosis (CVST).A total of 174 patients with CVST were recruited from the hospital between January 2006 and December 2017 and divided into two groups: (1) somatic cancer-related CVST group, defined as active somatic solid cancer patients with acute CVST; (2) cancer group (CG), defined as active somatic solid cancer patients without CVST. The cancer group patients were age and gender-matched somatic cancer-related CVST group patients. In addition, the types and amount distribution of cancer in cancer group were also matched with somatic cancer-related CVST group patients.Compared to cancer group patients, somatic cancer-related CVST group patients had more intracranial metastasis, a higher platelet count, higher plasma D-dimer, carcinoembryonic antigen (CEA) and cancer antigen (CA) 125 levels, a greater platelet to lymphocyte ratio (PLR), and a greater platelet to neutrophil ratio (PNR). The risk for CVST in somatic cancer-related CVST group patients increased independently by 0.7% (odds ratio [OR] 1.007; 95% confidence interval [CI] 1.000, 1.015; P = .047) with a 1 ng/ml increase in D-dimer levels, by 4.6% (OR 1.046; 95% CI 1.011, 1.083; P = .010) with a 1 U/ml increase in CEA, by 2.7% (OR 1.027; 95% CI 1.003, 1.051; P = .025) with a 1 U/ml increase in CA125, and by 10.6% (OR 1.106; 95% CI 1.002, 1.220; P = .045) with a 1 unit increase in PNR.It was suggested that together impacts of elevated plasma D-dimer, CA125, CEA levels, and a greater PNR may lead to hypercoagulability and to trigger the development of cancer-related CVST.

Near Infrared Spectroscopy Based Clinical Algorithm Applicability During Spinal Neurosurgery and Postoperative Cognitive Disturbances.

Background and Objectives: Postoperative cognitive disturbances (POCD) can significantly alter postoperative recovery. Inadequate intraoperative cerebral oxygen supply is one of the inciting causes of POCD. Near-infrared spectroscopy (NIRS) devices monitor cerebral oxygen saturation continuously and can help to guide intraoperative patient management. The aim of the study was to evaluate the applicability of the NIRS-based clinical algorithm during spinal neurosurgery and to find out whether it can influence postoperative cognitive performance. Materials and Methods: Thirty four patients scheduled for spinal neurosurgery were randomized into a study group (n = 23) and a control group (n = 11). We monitored regional cerebral oxygen saturation (rScO2) throughout surgery, using a NIRS device (INVOS 4100). If rScO2 dropped bilaterally or unilaterally by more than 20% from baseline values, or under an absolute value of 50%, the NIRS-based algorithm was initiated in the study group. In the control group, rScO2 was monitored blindly. To evaluate cognitive function, Montreal-Cognitive Assessment (MoCA) scale was used in both groups before and after the surgery. Results: In the study group, rScO2 dropped below the threshold in three patients and the NIRS-based algorithm was activated. Firstly, we verified correct positioning of the head; secondly, we increased mean systemic arterial pressure in the three patients by injecting repeated intravenous bolus doses of Ephedrine, ultimately resulting in an rScO2 increase above the approved threshold level. None of the three patients showed POCD. In the control group, one patient showed a drop in rScO2 of 34% from baseline and presented with a POCD. RScO2 drop occurred with other stable intraoperative measurements. Conclusions: A significant rScO2 drop may occur during spinal surgery in prone position despite other intraoperative measurements remaining stable, allowing it to stay otherwise unrecognized. Use of the NIRS-based clinical algorithm can help to avoid POCD in patients after spinal surgery.

Regeneration-associated cell transplantation contributes to tissue recovery in mice with acute ischemic stroke.

Various cell-based therapeutic strategies have been investigated for vascular and tissue regeneration after ischemic stroke. We have developed a novel cell population, called regeneration-associated cells (RACs), by quality- and quantity-controlled culture of unfractionated mononuclear cells. RACs were trans-arterially injected into 10-week-old syngeneic male mice at 1, 3, 5 or 7 days after permanent middle cerebral artery occlusion (MCAO) to determine the optimal timing for administration in terms of outcome at day 21. Next, we examined the effects of RACs injection at day 1 after MCAO on neurological deficits, infarct volume, and mediators of vascular regeneration and anti-inflammation at days 7 and 21. Infarct volume at day 21 was significantly reduced by transplantation of RACs at day 1 or 3. RACs injected at day 1 reduced the infarct volume at day 7 and 21. Angiogenesis and anti-inflammatory mediators, VEGF and IL-10, were increased at day 7, and VEGF was still upregulated at day 21. We also observed significantly enhanced ink perfusion in vivo, tube formation in vitro, and definitive endothelial progenitor cell colonies in colony assay. These results suggest that RAC transplantation in MCAO models promoted significant recovery of neural tissues through intensified anti-inflammatory and angiogenic effects.

Regional Cerebral Oxygen Saturation Decreases During Primary Hip Arthroplasty: An Analysis of Perioperative Regional Cerebral Oxygenation (rSO2), S100 Calcium-Binding Protein B (S100B) and Glial Fibrillary Acidic Protein (GFAP) Values. A Pilot Study.

BACKGROUND The incidence of postoperative cognitive dysfunction (POCD) after major joint arthroplasty is high. In the etiology of POCD, many factors have been cited, including thromboembolic complications. The incidence of cerebral embolization after lower extremity arthroplasty may be as high as 40-60%. The potential events of cerebral embolization could lead to a decrease in the regional cerebral oxygenation (rSO2) and increased serum levels of biochemical markers of brain damage. The objective of the study was to test whether there are any changes in the rSO2 values and serum markers of brain damage in patients who underwent total hip arthroplasty. MATERIAL AND METHODS Fifteen patients who underwent primary hip arthroplasty under spinal anesthesia were analyzed. The rSO2 was monitored using infrared spectroscopy. Biochemical analyses of S100 calcium-binding protein B (S100B) protein and fibrillary acidic protein (GFAP) serum concentrations were performed using immunoassay methods. RESULTS The values of rSO2 decreased during the surgery, but this was not related to mean arterial pressure variations or hemoglobin saturation. The concentration of S100B was increased compared to its preoperative values, and there were no changes in GFAP values. The changes in rSO2 readings correlated with the biomarkers' levels just after the surgery. CONCLUSIONS Our results suggest that S100B may be a more specific marker of astroglial damage in patients after primary total hip arthroplasty. The decrease in rSO2 readings may be due to micro-thromboembolic events that occurred during the surgery. However, the results of this study are preliminary, and further studies are needed to establish its clinical efficacy.

Non-pulsatile blood flow is associated with enhanced cerebrovascular carbon dioxide reactivity and an attenuated relationship between cerebral blood flow and regional brain oxygenation.

BACKGROUND: Systemic blood flow in patients on extracorporeal assist devices is frequently not or only minimally pulsatile. Loss of pulsatile brain perfusion, however, has been implicated in neurological complications. Furthermore, the adverse effects of absent pulsatility on the cerebral microcirculation are modulated similarly as CO2 vasoreactivity in resistance vessels. During support with an extracorporeal assist device swings in arterial carbon dioxide partial pressures (PaCO2) that determine cerebral oxygen delivery are not uncommon-especially when CO2 is eliminated by the respirator as well as via the gas exchanger of an extracorporeal membrane oxygenation machine. We, therefore, investigated whether non-pulsatile flow affects cerebrovascular CO2 reactivity (CVR) and regional brain oxygenation (rSO2). METHODS: In this prospective, single-centre case-control trial, we studied 32 patients undergoing elective cardiac surgery. Blood flow velocity in the middle cerebral artery (MCAv) as well as rSO2 was determined during step changes of PaCO2 between 30, 40, and 50 mmHg. Measurements were conducted on cardiopulmonary bypass during non-pulsatile and postoperatively under pulsatile blood flow at comparable test conditions. Corresponding changes of CVR and concomitant rSO2 alterations were determined for each flow mode. Each patient served as her own control. RESULTS: MCAv was generally lower during hypocapnia than during normocapnia and hypercapnia (p < 0.0001). However, the MCAv/PaCO2 slope during non-pulsatile flow was 14.4 cm/s/mmHg [CI 11.8-16.9] and 10.4 cm/s/mmHg [CI 7.9-13.0] after return of pulsatility (p = 0.03). During hypocapnia, non-pulsatile CVR (4.3 ± 1.7%/mmHg) was higher than pulsatile CVR (3.1 ± 1.3%/mmHg, p = 0.01). Independent of the flow mode, we observed a decline in rSO2 during hypocapnia and a corresponding rise during hypercapnia (p < 0.0001). However, the relationship between ΔrSO2 and ΔMCAv was less pronounced during non-pulsatile flow. CONCLUSIONS: Non-pulsatile perfusion is associated with enhanced cerebrovascular CVR resulting in greater relative decreases of cerebral blood flow during hypocapnia. Heterogenic microvascular perfusion may account for the attenuated ΔrSO2/ΔMCAv slope. Potential hazards related to this altered regulation of cerebral perfusion still need to be assessed. TRIAL REGISTRATION: The study was retrospectively registered on October 30, 2018, with Clinical Trial.gov (NCT03732651).

Pre-stroke surgery is not beneficial to normotensive rats undergoing sixty minutes of transient focal cerebral ischemia.

Experimental stroke in rodents, via middle cerebral artery occlusion (MCAO), can be associated with a negative impact on wellbeing and mortality. In hypertensive rodents, pre-stroke craniotomy increased survival and decreased body weight loss post-MCAO. Here we determined the effect, in normotensive Sprague-Dawley rats following 60 minutes MCAO, with or without pre-surgical craniotomy, on post-stroke outcomes in terms of weight loss, neurological deficit, lesion volume and functional outcomes. There was no effect of pre-stroke craniotomy on indicators of wellbeing including survival rate (P = 0.32), body weight loss (P = 0.42) and neurological deficit (P = 0.75). We also assessed common outcome measures following experimental stroke and found no effect of pre-stroke craniotomy on lesion volume as measured by T2-weighted MRI (P = 0.846), or functional performance up to 28 days post-MCAO (staircase test, P = 0.32; adhesive sticker test, P = 0.49; cylinder test, P = 0.38). Thus, pre-stroke craniotomy did not improve animal welfare in terms of body weight loss and neurological deficit. However, it is important, given that a number of drug delivery studies utilise the craniotomy procedure, to note that there was no effect on lesion volume or functional outcome following experimental stroke.

3-Methylcholanthrene/Aryl-Hydrocarbon Receptor-Mediated Hypertension Through eNOS Inactivation.

Endothelial nitric oxide synthase (eNOS) modulates vascular blood pressure and is predominantly expressed in endothelial cells and activated through the protein kinase B (Akt/PKB)-dependent pathway. We previously reported that 3-methylcholanthrene (3MC) activates the aryl hydrocarbon receptor (AhR) and reduces PI3K/Akt phosphorylation. This study investigated the mechanism underlying the downregulatory effects of 3-MC on nitric oxide (NO) production occurring through the AhR/RhoA/Akt-mediated mechanism. The mechanism underlying the effects of 3-MC on eNOS activity and blood pressure was examined in vitro and in vivo through genetic and pharmacological approaches. Results indicated that 3-MC modified heat shock protein 90 (HSP90), caveolin-1, dynein, and eNOS mRNA and protein expression through the AhR/RhoA-dependent mechanism in mouse cerebral vascular endothelial cells (MCVECs) and that 3-MC reduced eNOS phosphorylation through the AhR/RhoA-mediated inactivation of Akt1. The upregulation of dynein expression was associated with decreased eNOS dimer formation (eNOS dimer; an activated form of the enzyme). Coimmunoprecipitation assay results indicated that 3-MC significantly reduced the interaction between eNOS and its regulatory proteins, including Akt1 and HSP90, but increased the interaction between eNOS and caveolin-1. Immunofluorescence and Western blot analysis revealed that 3-MC reduced the amount of membrane-bound activated eNOS, and a modified Griess assay revealed that 3-MC concomitantly reduced NO production. However, simvastatin reduced 3-MC-mediated murine hypertension. Our study results indicate that AhR, RhoA, and eNOS have major roles in blood pressure regulation. Statin intervention might provide a potential therapeutic approach for reducing hypertension caused by 3-MC. J. Cell. Physiol. 232: 1020-1029, 2017. © 2016 Wiley Periodicals, Inc.

Neuroprotective Effect of Antioxidants and Moderate Hypoxia as Combined Preconditioning in Cerebral Ischemia.

We studied combined effect of moderate hypoxia and compounds pQ-4, pQ-915, pQ-1032, and pQ-1104 on neurological deficit and survival of rats after bilateral ligation of common carotid arteries. Preconditioning including moderate hypoxia and treatment with compound pQ-4 produced a neuroprotective effect and increased animal survival during the early (by 51%) and late (by 33.5%) periods of modeled ischemia and reduced neurological deficit (by 50% and 41%, respectively). Moreover, this combination of preconditioning factors prevented postischemic excessive activation of free radical oxidation in brain hemispheres and blood serum.

O papel do DOPPLER da artéria cerebral média nos fetos com Crescimento Restrito Tardio / The role of middle cerebral artery Doppler in late onset fetal growth restriction

Ocrescimento intrauterino restrito (CIUR) é uma inibição patológica do crescimento fetal, acometendo 5-10% das gestações e está associado ao aumento da morbimortalidade perinatal. Este estudo tem como objetivo realizar uma revisão não sistemática sobre os eventos adversos perinatais dos fetos com CIUR tardio e alteração seletiva do Doppler da artéria cerebral média (ACM). A pesquisa bibliográfica foi realizada através da base de dados do PubMed, obtendo um total de 25 referências, que serviram de base para o presente artigo. Conclui-se que a artéria cerebral média possui valor particular na identificação e predição de resultados adversos nestes fetos, os quais possuem risco aumentado de desenvolvimento neurológico anormal ao nascimento e aos dois anos de idade.(AU)

Intrauterine growth restriction (IUGR) is a pathological inhibition of the fetal growth that affects 5-10% of pregnancies and it is associated with an increase of perinatal morbidity and mortality. This study aims to conduct a non-systematic review of perinatal adverse events of fetuses with late-onset IUGR and selective changes in middle cerebral artery (MCA) Doppler. A literature search was performed using the PubMed database. A total of 25 references, which were the basis for this article was obtained. It concludes the middle cerebral artery has a particular value in the identification and prediction of adverse outcomes in these fetuses, which has an increased risk of abnormal neurological performance at birth and at two years of age.(AU)

Cortical branches of the middle cerebral artery in silver fox (Vulpes vulpes)

The study of the vascularization of the cerebrum in silver fox was performed on 80 cerebral hemispheres. It was found that the middle cerebral artery is the strongest vessel supplying blood to the cerebrum. The artery gets divided into ten permanent branches. Two olfactory arteries supply the region of the cerebrum located on the border between the old and the new cortex. The other eight supply the region of the new cortex. The frontal, parietal and temporal branches descended independently from the main trunk of the middle cerebral artery or formed a common trunk. Common trunks for respective groups of branches have been described as the anterior, superior and posterior middle cerebral artery. The alterior olfactory artery in 5% of cases and posterior olfactory artery in 2.5% of cases were independent branches of the middle cerebral artery extending from the rostral cerebral artery.(AU)

Cerebral oximetry as a biomarker of postoperative delirium in cardiac surgery patients.

PURPOSE: A promising monitoring strategy for delirium is the use of cerebral oximetry, but its validity during delirium is unknown. We assessed the relationship between oximetry and delirium. We hypothesized that as cerebral oximetry values increased, delirium would resorb. MATERIALS AND METHODS: An observational study was conducted with 30 consecutive adults with delirium after cardiac surgery. Oximetry, delirium assessments, and clinical data were collected for 3 consecutive days after delirium onset. Oximetry was obtained using near-infrared spectroscopy. Delirium was assessed using diagnosis, occurrence (Confusion Assessment Method-ICU), and severity scales (Delirium Index). RESULTS: All patients presented delirium at entry. The mean oximetry value decreased from 66.4±6.7 (mean±SD) to 50.8±6.8 on the first day after delirium onset and increased in patients whose delirium resorbed over the 3 days. The relationship between oximetry, delirium diagnosis, and severity was analyzed with a marginal model and linear mixed models. Cerebral oximetry was related to delirium diagnosis (P≤.0001) and severity (P≤.0001). CONCLUSION: This study highlighted the links between increased cerebral oximetry values and delirium resorption. Oximetry values may be useful in monitoring delirium progression, thus assisting in the management of this complicated condition.